Disorders Associated with the Immune System Ch 19 We’ll discuss: - Hypersensitivity: - Type I: - reactions - systemic vs. localized - desensitization - Type II: - blood types - Cancer - AIDS
Disorders Associated with the Immune System
Ch 19
We’ll discuss:- Hypersensitivity:
- Type I: - reactions- systemic vs. localized- desensitization
- Type II:- blood types
- Cancer- AIDS
Hypersensitivity
Type of Reaction Time After Exposure for Clinical Symptoms
Type I (anaphylactic) <30 min Type II (cytotoxic) 5–12 hours Type III (immune complex) 3–8 hours Type IV (delayed cell-mediated) ≥1 day
Figure 19.1a
Granule
Histamine andother mediators
Mast cell orbasophil
AntigenIgE
Hypersensitivity
Figure 19.1b
Mast cellsHypersensitivity
Figure 19.2
Hypersensitivity - Localized
Figure 19.3
Hypersensitivity - Desensitization
Table 17.1
Hypersensitivity - Desensitization
Insert Table 19.2
Hypersensitivity – Blood types
Hypersensitivity – Blood types
Hypersensitivity – Blood types
If the woman becomes pregnant with another Rh+ fetus, her anti-Rhantibodies will cross the placenta and damage fetal red blood cells.
Figure 19.4
In response to the fetal Rh antigens, the mother will produce anti-Rhantibodies.
Rh– mother carrying her first Rh+ fetus. Rh antigens from the developing fetus can enter the mother's blood during delivery.
Rh+ father.
Placenta
Hypersensitivity – Blood types
Figure 19.11
The small CTL hasalready made aperforation in thecancer cell.
The cancer cell has disintegrated.
CTL
Cancer cell Remains of cancer cell
CTL
Cancer
Cancer
What is PROVENGE and how does it work?
PROVENGE (sipuleucel-T) is an autologous cellular immunotherapy designed to stimulate a patient’s own immune system against cancer. PROVENGE is manufactured in several steps. First the patient’s blood is run through a machine in a process known as leukapheresis. During the process, some of the patient’s immune cells are collected. These immune cells are then exposed to a protein intended to stimulate and direct them against prostate cancer. Following this exposure, the activated immune cells are then returned to the patient to treat the prostate cancer.
PROVENGE is administered intravenously in a three-dose schedule at approximately two week intervals. Each dose is preceded by the leukapheresis procedure approximately three days prior to the scheduled treatment, and is administered only to the patient from whom the cells were obtained.
What are the ingredients in PROVENGE?
The active components of PROVENGE are autologous antigen presenting cells (APCs) and the protein called PAP-GM-CSF. APCs are activated during a defined culture period with a recombinant human protein, PAP-GM-CSF, consisting of prostatic acid phosphatase (PAP), an antigen expressed in prostate cancer tissue, linked to granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune cell activator.
The cellular composition of PROVENGE will vary, depending on the cells obtained from the individual patient during leukapheresis. In addition to the APCs, the product also contains T cells, B cells, natural killer (NK) cells, and other cells.
Each dose of PROVENGE is suspended in 250 mL of Lactated Ringer’s Injection, USP in a sealed, patient-specific infusion bag.
PROVENGE contains no preservatives or adjuvants. fda.gov
Cancer
Insert Fig 19.16
Figure 19.16
Years (for someone not receiving anti-HIV medication)3
mo6
mo1 2 3 4 5 6 7 8 9 10
1
2
3
4
5
6
7
8
9
10
11
12
CD
4+T
cell
bloo
d co
ncen
trat
ion
(cel
ls/μ
l)
Blo
od p
lasm
a H
IV/R
NA
(mill
ions
of c
opie
s/m
l)
100
200
300
400
500
600
700
800
900
1000
1100
1200
AIDS
Insert Fig 19.17
Figure 19.17 Distribution of HIV infection and AIDS in regions of the world.
WESTERN EUROPE
EASTERN EUROPE &CENTRAL ASIA EAST ASIA*
SOUTH &SOUTHEAST ASIA*
770,000
4.1 millionAUSTRALIA,
NEW ZEALAND& OCEANIA
57,000
SUB-SAHARAN AFRICA
22.5 million
NORTH AFRICA &THE MIDDLE EAST
460,000
1.4 million820,000
1.4 million
LATIN AMERICA
CARIBBEAN
240,000
1.5 million
NORTH AMERICA
Estimates are that India now hasabout 2.4 million cases; Chinais estimated to have less than1 million cases.
*
= 100,000 persons living with HIV/AIDS
AIDS
TED talk: “Hans Rosling: Insights on HIV, in stunning data visuals”https://www.ted.com/talks/hans_rosling_the_truth_about_hiv?language=en#t-570752
AIDS
Insert Fig 20.16a
Figure 20.16a
Acyclovir structurally resembles the nucleoside deoxyguanosine.
Deoxyguanosine Acyclovir
Guanine
AIDS
Figure 20.16bc
Phosphate
Nucleoside
The enzyme thymidine kinase combines phosphates with nucleosides to form nucleotides, which are then incorporated into DNA.
Guaninenucleotide
Normal thymidine kinase
DNA polymerase Incorporated into DNA
Acyclovir has no effect on a cell not infected by a virus, that is, with normal thymidine kinase. In a virally infected cell, the thymidine kinase is altered and converts the acyclovir (which resembles the nucleoside deoxyguanosine) to a false nucleotide, which blocks DNA synthesis by DNA polymerase.
PhosphateDNA polymerase blocked by false nucleotide. Assembly of DNA stops.
False nucleotide(acyclovir triphosphate)
Acyclovir (resembles nucleoside)
Thymidine kinase in virus-infected cell
AIDS